Cavitation damage during sonothrombolysis using high intensity focused ultrasound.

Abstract

High intensity focused ultrasound (HIFU) has been shown to accelerate thrombolysis, in vitro and in vivo, for treatment of ischemic stroke. Stable and inertial cavitations are thought to play an important role in sonothrombolysis, even though the mechanisms are not fully understood. Possible mechanisms associated with both stable cavitation (i.e., microstreaming) and inertial cavitation (i.e., microjets) are thought to increase clot lysis by enhancing the delivery of a thrombolytic agent. The damage to a blood clot\textquoteright{}s fiber network from bubble collapses in an HIFU field is studied. The region of damage caused by a single bubble collapse on the fiber network of the blood clot exposed to HIFU is estimated and compared with experimental assessment of the damage. The mechanical damage to the network is estimated using two independent approaches: a fiber deformation based method and an energy based method. Whole human blood clots under flow conditions are exposed to 220 kHz ultrasound using the ExAblate 4000. During HIFU exposure, passive cavitation detection is performed using a wide band (10 kHz–15 MHz) hydrophone. Scanning electron microscopy is used to assess the region of damage experimentally. [Work supported in part by NSF Graduate Research Fellowship.]